Polychlorinated biphenyls, cytochrome P4501A1 polymorphism, and postmenopausal breast cancer risk
| Autor: | K B, Moysich, P G, Shields, J L, Freudenheim, E F, Schisterman, J E, Vena, P, Kostyniak, H, Greizerstein, J R, Marshall, S, Graham, C B, Ambrosone |
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| Rok vydání: | 1999 |
| Předmět: |
Chromatography
Gas Lung Neoplasms Genotype New York Breast Neoplasms Polymerase Chain Reaction Body Mass Index Risk Factors Confidence Intervals Cytochrome P-450 CYP1A1 Odds Ratio Humans Isoleucine Polycyclic Aromatic Hydrocarbons Alleles Aged Polymorphism Genetic Homozygote Valine Exons Lipids Polychlorinated Biphenyls Postmenopause Logistic Models Case-Control Studies Body Burden Environmental Pollutants Female Steroids Polymorphism Restriction Fragment Length |
| Zdroj: | Cancer epidemiology, biomarkersprevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 8(1) |
| ISSN: | 1055-9965 |
| Popis: | In experimental systems, polychlorinated biphenyls (PCBs) induce cytochrome P4501A1 (CYP1A1), which is involved in metabolism of steroid hormones and polycyclic aromatic hydrocarbons in humans. A genetic polymorphism coding for a valine to isoleucine substitution in exon 7 has been associated with lung cancer risk in Japanese populations. In a previous study, we found no association between CYP1A1 genotype and breast cancer risk. However, we were interested in determining whether genotype would relate to risk when PCB body burden was taken into account. In a subset of a case-control study in western New York, 154 postmenopausal women with incident, primary, histologically confirmed postmenopausal breast cancer and 192 community controls were interviewed and underwent phlebotomy. Serum levels of 56 PCB peaks were determined by high resolution gas chromatography with electron capture. PCR-RFLP analyses of the CYP1A1 polymorphism were performed. Unconditional logistic regression was used to compute adjusted odds ratios and 95% confidence intervals. Among women with serum PCB levels above the median of the distribution in the control group, there was increased risk of breast cancer associated with the presence of at least one valine allele, compared with women who were homozygous for the isoleucine alleles (odds ratio, 2.93; 95% confidence interval, 1.17-7.36). Among women with low PCB body burden, no association between CYP1A1 genotype and breast cancer risk was observed. Adjustment for serum lipids and body mass index did not affect the magnitude of the observed associations. PCB body burden may modify the effect of the polymorphism on postmenopausal breast cancer risk through increased CYP1A1 enzyme induction or by activation by specific PCB congeners. These results should be considered preliminary, pending replication by other studies. |
| Databáze: | OpenAIRE |
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